AB0492 INTESTINAL MICROBIOLOGICAL DISORDER CLOSELY ASSOCIATED WITH PERIPHERAL LYMPHOCYTE SUBSETS AND CYTOKINES IN SYSTEMIC LUPUS ERYTHEMATOSUS.
Authors: R. Zhao, S. X. Zhang, J. Qiao, S. Song, T. Cheng, X. Li
Journal: Annals of the Rheumatic Diseases (2022)

Background Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by widespread inflammation and tissue damage in multiple organs[1]. Microbiome is one of environmental factors that has been suggested to contribute to the occurrence and development of SLE[2]. Objectives This study aims to the understanding of the pathogenesis of SLE from the perspective of intestinal microorganisms and investigate the associations between flora and peripheral lymphocyte subpopulations and cytokines in SLE patients. Methods Fecal samples were collected from 96 patients with SLE, and 96 sex-and age-matched healthy controls (HCs). The gut microbiota were investigated via 16s rRNA sequencing and the peripheral T lymphocyte subsets of these participants were assessed by flow cytometry. Indicators of disease activity such as erythrocyte sedimentation rate (ESR), C-reaction protein (CRP), complement C3 and C4 were recorded. Differential abundance analysis was carried out using the edgeR algorithm. The Wilcoxon rank-sum test was used to compare alpha diversity indices, bacterial abundances, and the F/B ratio between groups. R (version 4.0.1) was used for comparative statistics, and pearson’s correlation analysis was used to assess the correlations between the relative abundances of bacterial genera and serum levels of ESR, CRP, C3 and C4 in the samples; correlations with p &lt; 0.05 were considered significant. Results The alpha estimators of richness (ACE and Chao 1) were significantly reduced in SLE feces samples compared with those of HCs (p &lt; 0.0001). Bacterial diversity estimators, including the Shannon (p &lt; 0.001) and Simpson’s (p &lt; 0.01) indices, were also significantly lower in SLE (Figure 1 A-D ). The microbial community structures of the SLE and HCs could be separated by unweighted UnFrac-based principal coordinates analysis (PCoA) (R = 0.186, and p = 0.001; Figure 1 E ). Significant differences in gut microbiota composition between SLE and HCs were found using the edgeR algorithm. Compared with HCs, 24 species of flora were discovered to be distinctly different(p &lt; 0.05). Moreover, there was a significant positive correlation between Tregs and Corynebacterium(p &lt; 0.05), CD8+T and Corynebacterium (p &lt; 0.05), CD4+T and Corynebacterium (p &lt; 0.05), T and Corynebacterium (p &lt; 0.05), Th1 and Escherichia−Shigella (p &lt; 0.01), Th2 and Dielma (P&lt;0.001) as well as Eubacterium eligens group (p &lt; 0.05), NK and Faecalibacterium (p &lt; 0.01). as well as Corynebacterium (p &lt; 0.001), IL-6 and Coprococcus (p &lt; 0.05), IL-10 and Eubacterium eligens group (p &lt; 0.001) as well as Veillonella (p &lt; 0.05). and Lachnospira (p &lt; 0.01). As for clinical disease measures, there were positive correlations between CRP and Eubacterium ventriosum (p &lt; 0.05). and Coprococcus (p &lt; 0.05), C4 and the abundance of Corynebacterium (p &lt; 0.05) (Figure 1 F ). Conclusion Patients with gut dysbiosis that mainly characterized by reduced the diversity and impaired abundance of the intestinal flora. Abnormality of T cell subsets and cytokines, especially the level of CD4+T, CD8+T, NK, Treg, Th, IL-6 and IL-10 cells contributes to the occurrence and progression of SLE, which may be related to the disturbance of gut microbiota. The discovery of the associated intestinal microbiota of SLE may provide a new idea for treatment. References [1]Fava A, Petri M. Systemic lupus erythematosus: diagnosis and clinical management. J Autoimmun. (2019) 96:1–13. 10.1016/j.jaut.2018.11.001 [2]He Z, Shao T, Li H, Xie Z, Wen C: Alterations of the gut microbiome in Chinese patients with systemic lupus erythematosus. Gut pathogens 2016, 8:64. Acknowledgements This work was supported by the National Natural Science Foundation of China (No. 82001740). Disclosure of Interests None declared